Project Summary Cancer cachexia is a devastating syndrome resulting from the wasting of peripheral tissues as a result of pathophysiological interactions between tumors and distant tissues. Although ~80% of cancer patients suffer from cachexia and has been implicated in ~25% of death in cancer patients, there is no approved therapeutics to combat this deadly disease. Part of the reasons for limited progress in cancer cachexia is because we know little about the underlying molecular mechanisms on how tumor induces cachexia through long- range interactions. During my postdoctoral studies, I propose a number of studies that will provide mechanistic insights into how ImpL2 and other tumor-secreted factors are regulated to modulate organ wasting. In Aim1, I will dissect which tumorigenic pathways regulate ImpL2. In Aim 2, I will utilize targeted DamID technique to identify other tumor-derived factors that affect distant tissue homeostasis relevant for organ wasting. Finally, in Aim 3, I will explore whether other conditions that induce organ wasting interact with ImpL2-dependent signaling. Together, these studies will identify regulatory networks orchestrating organ wasting in pathological conditions and also provide novel insights into potential therapeutic targets for organ wasting.